1. Field of the Invention
The present invention relates to the treatment of benign pigmented moles (naevi) of the skin and mucous membranes; in particular nevus cell nevi, of lentigos and pigmented nevi of the mucous membranes with locally applied, but in particular with topical formulations. Furthermore, it relates to topical formulations which are suitable for this purpose.
2. Discussion of Background Information
The term nevus cell nevi means different benign skin changes, pigmented moles (birthmark, liver spot) that are composed in cellular terms of so-called nevus cells. Nevus cells are a defective development of the normal pigment-forming cells, the melanocytes. Melanocytic nevi occur in different number, size and color intensity in virtually all human beings. The outward appearance of nevi can be very different. They can be pigmented moles lying at the skin level or raised above the skin level (rounded, pediculate or flat) punctiform but also large-scale, wart-like, uneven or smooth, and the color ranges from skin-colored to brown to black. The number of melanocytic nevi acquired increases over the course of life. Nevus cell nevi with conspicuous structure have an increased risk of degeneration and are called dysplastic or atypical nevus cell nevi.
A malignant melanoma, that is black skin cancer, may possibly develop from a nevus cell nevus. In over 60 percent of all cases it develops from a nevus cell nevus. In recent decades a clear increase in the incidence of melanoma has been registered. While in the U.S. in 1960 a lifetime risk of approx. 1:600 was assumed, today one of 1:100 is observed. Thus, according to Dr. Matthias Volkenandt (Clinic for Dermatology and Allergiology of Ludwig-Maximilian University, Munich, Frauenlobstrasse 9, 80337 Munich), for example, melanoma has an incidence in the region of Bavaria of approx. 14 (i.e., 14 new cases) per 100,000 inhabitants a year. This corresponds to a lifetime risk of approx. 1% (every 100th person will be diagnosed with a melanoma in the course of his/her life). Given this figure, melanoma is not the most frequent tumor in humans, but the rise in the incidence according to Volkenandt is greater than with any other tumor.
According to the current level of knowledge, there is no preventative treatment or therapy that combats the degeneration of nevus cell nevi. Nevi with an increased risk of degeneration are chiefly surgically removed. Laser treatment plays more of a role in cosmetic aspects. Both methods are invasive, associated with certain risks (scarring, skin discoloration, etc.) and high costs.
The development of an acquired nevus is always preceded by a small, sometimes microscopically small, red spot (a bleeding or hemangioma). From this nevus precursor a larger red, somewhat raised mole frequently develops. From the nevus precursors then the brown nevus cell nevi develop, of different size, brown color and structure.
Artemisinine (also called qinghaosu) is a sesquiterpene lactone with a peroxide group, which has hitherto been examined and used mainly as a systematically active antimalarial drug. Artemisinine is very hard to dissolve in water; however, water-soluble derivatives of artemisinine have been developed. The systemic or topical use of artemisinine and derivatives thereof for the treatment of psoriasis, diseases of viral origin (warts, molluscum contagiosum and ovinia), ultraviolet radiation-induced diseases (polymorphous light dermatosis, “collagen vascular disease”, premalignant keratosis, Bowen syndrome, lentigo maligna, basal-cell carcinoma, squamous cell carcinoma and malignant melanoma), vesicular skin diseases and hemorrhoids is described in EP-A-O 428 773.